PubMed Health⌕ Search

Biomedical subjects

C Wrutniak-Cabello

Publications and source records attributed to C Wrutniak-Cabello.

7 recordsLinked to original sources
PubMed2001

Opposing functions of ATF2 and Fos-like transcription factors in c-Jun-mediated myogenin expression and terminal differentiation of avian myoblasts.

With the aim to identify the oncoprotein partners implicated in the c-Jun myogenic influence, we carried out stable transfection experiments of c-Jun and/or ATF2, Fra2, c-Fos overexpression in avian myoblasts. Before induction of differentiation, c-Jun repressed myoblast withdrawal from the cell cycle, as did a TPA treatment. However, after serum removal, unlike TPA, c-Jun significantly stimulated myoblast differentiation. In search for specific partners involved in this dual influence, we found that a reduction in the amounts of c-Fos and Fra2 and an increase in c-Jun proteins occurred at cell confluence, a situation likely to favor cooperation between c-Jun and ATF2 during terminal differentiation. Whereas c-Fos and Fra2 cooperated with c-Jun to abrogate myoblast withdrawal from the cell cycle and terminal differentiation, ATF2 co-expression potentiated the positive myogenic c-Jun influence. In addition, myogenin expression was a positive target of this cooperation and this regulation occurred through a stimulation of myogenin promoter activity: (1) whereas c-Fos or Fra2 co-expression abrogated c-Jun stimulatory activity on this promoter, ATF2 co-expression potentiated this influence; (2) using a dominant negative ATF2 mutant, we established that c-Jun transcriptional activity required functionality of endogenous ATF2. These data suggest that through this dual myogenic influence due to cooperations with different partners, c-Jun is involved in the control of duration of myoblast proliferation and thereafter of fusion efficiency.

Activating Transcription Factor 2↗
PubMed2001

The triiodothyronine nuclear receptor c-ErbAalpha1 inhibits avian MyoD transcriptional activity in myoblasts.

Thyroid hormone stimulates myoblast differentiation, through an inhibition of AP-1 activity occurring at the onset of differentiation. In this study we found that the T3 nuclear receptor c-ErbAalpha1 (T3Ralpha1) is involved in a mechanism preserving the duration of myoblast proliferation. Independently of the hormone presence, T3Ralpha1 represses avian MyoD transcriptional activity. Using several mutants of T3Ralpha1, we found that the hinge region plays a crucial role in the inhibition of MyoD activity. In particular, mutations of two small basic sequences included in alpha helices abrogate the T3Ralpha1/MyoD functional interaction. Similarly, the T3 receptor also represses myogenin transcriptional activity. Therefore, despite stimulating avian myoblast differentiation by a T3-dependent pathway not involving myogenic factors, T3Ralpha1 contributes to maintain an optimal myoblast proliferation period by inhibiting MyoD and myogenin activity.

Animals↗
PubMed2001

Identification of functional domains involved in BTG1 cell localization.

We have previously shown that BTG1 stimulates myoblast differentiation. In addition, this protein displays a major nuclear localization in confluent myoblasts, decreasing during the early steps of differentiation, and is essentially detected in the cytoplasm of mature myotubes. To identify the domains involved in the cellular trafficking of BTG1, we observed the localization of several BTG1 sequences fused to betaGalactosidase. The highly conserved B box among all members of the BTG family induces a significant nuclear localization of the betaGal moiety, enhanced by presence of the BTG1 carboxy-terminal sequence. In addition, a functional Nuclear Export Signal (NES) overlaps the B box. Moreover, presence of the first 43 NH(2)-terminal amino acids reduced the nuclear localization of each chimeric protein tested. Last, the BTG1 amino-terminal domain bears an LxxLL motif favouring nuclear accumulation, and another region encompassing the A box inhibiting nuclear localization. In contrast to a BTG1 mutant exclusively localized in the cytoplasm, transient expression of a mutant displaying a nuclear localization enhanced myoblasts withdrawal from the cell cycle and terminal differentiation, thus mimicking the myogenic influence of BTG1. In conclusion, several regions of BTG1 are implicated in its cellular localization, and BTG1 myogenic activity is induced at the nuclear level.

Active Transport, Cell Nucleus↗
PubMed2001

Thyroid hormone action in mitochondria.

Triiodothyronine (T3) is considered a major regulator of mitochondrial activity. In this review, we show evidence of the existence of a direct T3 mitochondrial pathway, and try to clarify the respective importance of the nuclear and mitochondrial pathways for organelle activity. Numerous studies have reported short-term and delayed T3 stimulation of mitochondrial oxygen consumption. Convincing data indicate that an early influence occurs through an extra-nuclear mechanism insensitive to inhibitors of protein synthesis. Although it has been shown that diiodothyronines could actually be T3 mediators of this short-term influence, the detection of specific T3-binding sites, probably corresponding to a 28 kDa c-Erb Aalpha1 protein of the inner membrane, also supports a direct T3 influence. The more delayed influence of thyroid hormone upon mitochondrial respiration probably results from mechanisms elicited at the nuclear level, including changes in phospholipid turnover and stimulation of uncoupling protein expression, leading to an increased inner membrane proton leak. However, the involvement of a direct mitochondrial T3 pathway leading to a rapid stimulation of mitochondrial protein synthesis has to be considered. Both pathways are obviously involved in the T3 stimulation of mitochondrial genome transcription. First, a 43 kDa c-Erb Aalpha1 protein located in the mitochondrial matrix (p43), acting as a potent T3-dependent transcription factor of the mitochondrial genome, induces early stimulation of organelle transcription. In addition, T3 increases mitochondrial TFA expression, a mitochondrial transcription factor encoded by a nuclear gene. Similarly, the stimulation of mitochondriogenesis by thyroid hormone probably involves both pathways. In particular, the c-erb Aalpha gene simultaneously encodes a nuclear and a mitochondrial T3 receptor (p43), thus ensuring coordination of the expression of the mitochondrial genome and of nuclear genes encoding mitochondrial proteins. Recent studies concerning the physiological importance of the direct mitochondrial T3 pathway involving p43 led to the conclusion that it is not only involved in the regulation of fuel metabolism, but also in the regulation of cell differentiation. As the processes leading to or resulting from differentiation are energy-consuming, p43 coordination of metabolism and differentiation could be of significant importance in the regulation of development.

Animals↗
PubMed2000

New molecular aspects of regulation of mitochondrial activity by fenofibrate and fasting.

Fenofibrate and fasting are known to regulate several genes involved in lipid metabolism in a similar way. In this study measuring several mitochondrial enzyme activities, we demonstrate that, in contrast to citrate synthase and complex II, cytochrome c oxidase (COX) is a specific target of these two treatments. In mouse liver organelles, Western blot experiments indicated that mitochondrial levels of p43, a mitochondrial T3 receptor, and mitochondrial peroxisome proliferator activated receptor (mt-PPAR), previously described as a dimeric partner of p43 in the organelle, are increased by both fenofibrate and fasting. In addition, in PPAR alpha-deficient mice, this influence was abolished for mt-PPAR but not for p43, whereas the increase in COX activity was not altered. These data indicate that: (1) PPAR alpha is involved in specific regulation of mt-PPAR expression by both treatments; (2) fenofibrate and fasting regulate the mitochondrial levels of p43 and thus affect the efficiency of the direct T3 mitochondrial pathway.

Animals↗
PubMed2000

A 45 kDa protein related to PPARgamma2, induced by peroxisome proliferators, is located in the mitochondrial matrix.

Besides their involvement in the control of nuclear gene expression by activating several peroxisome proliferator-activated receptors (PPARs), peroxisome proliferators influence mitochondrial activity. By analogy with the previous characterization of a mitochondrial T3 receptor (p43), we searched for the presence of a peroxisome proliferator target in the organelle. Using several antisera raised against different domains of PPARs, we demonstrated by Western blotting, immunoprecipitation and electron microscopy experiments, that a 45 kDa protein related to PPARgamma2 (mt-PPAR) is located in the matrix of rat liver mitochondria. In addition, we found that the amounts of mt-PPAR are increased by clofibrate treatment. Moreover, in EMSA experiments mt-PPAR bound to a DR2 sequence located in the mitochondrial D-loop, by forming a complex with p43. Last, studies of tissue-specific expression indicated that mt-PPAR is detected in mitochondria of all tissues tested except the brain in amounts positively related to p43 abundance. Besides their involvement in the control of nuclear gene expression by activating several peroxisome proliferator-activated receptors (PPARs), peroxisome proliferators influence mitochondrial activity. By analogy with the previous characterization of a mitochondrial T3 receptor (p43), we searched for the presence of a peroxisome proliferator target in the organelle. Using several antisera raised against different domains of PPARs, we demonstrated by Western blotting, immunoprecipitation and electron microscopy experiments, that a 45 kDa protein related to PPARgamma2 (mt-PPAR) is located in the matrix of rat liver mitochondria. In addition, we found that the amounts of mt-PPAR are increased by clofibrate treatment. Moreover, in EMSA experiments mt-PPAR bound to a DR2 sequence located in the mitochondrial D-loop, by forming a complex with p43. Last, studies of tissue-specific expression indicated that mt-PPAR is detected in mitochondria of all tissues tested except the brain in amounts positively related to p43 abundance.

Animals↗